- Assistant Professor, The Ben May Department for Cancer Research, Committee on Cancer Biology
Ph.D., Cornell University, 2006
The skin epidermis and its appendages provide a protective barrier that keeps harmful microbes out and essential body fluids in. To perform these functions while confronting the harsh physicochemical traumas from the outside world, our skin must undergo rejuvenation through homeostasis and wound repair. Both processes rely on the activities of skin stem cells, including the activation and migration of stem cells upon wounding and the delicate balance of stem cell proliferation, self-renew and differentiation during tissue homeostasis. Understanding the underlying mechanisms is particularly important, as these processes, when gone awry, lead to skin diseases including cancers.
One pilo-sebaceous unit in mammalian skin contains a hair follicle, sebaceous gland, and interfollicular epidermis. In adult animals, the resident population of somatic stem cells in the hair follicle has been well defined. They reside in a specific niche called the bulge that is located at the upper portion of hair follicle. These cells allow the hair follicle to continuously cycle through different stages of anagen (active growth), catagen (regression phase) and telogen (rest phase). Quiescent bulge stem cells become activated at the start of anagen. Activated stem cells migrate downward to produce highly proliferative matrix cells at the base of the hair follicle. Matrix cells further differentiate to form different cell types that create a functional hair follicle. When wounding perturbs epidermal homeostasis by cell depletion, it mobilizes bulge stem cells, which migrate upward to re-epithelialize injured epidermis. Together, the functional importance and technical accessibility have made hair follicles an excellent model system for studying somatic stem cells during tissue homeostasis or upon pathological stimulation.
Like other somatic stem cells, follicle stem cells reside in a specific tissue microenvironment or niche, bulge. Physicochemical cues present in the niche tightly regulate the functions of bulge stem cells. In skin, constant mechanical stress promotes cells to develop an elaborate cytoskeletal system connecting to specialized cellular adhesions. Different cytoskeletons in skin interact and coordinate their dynamics, conferring the essential mechanical strength to skin and enabling skin cells to form adhesive sheets of resilient tissue. The overall goal of our research is to determine the role of cytoskeletal dynamics in transmitting the niche signals to regulate skin somatic stem cell activity and functions. Our research will greatly advance our understanding of the mechanisms regulating human stem cells, and potentially lead to the development of novel and effective therapeutic treatments for various human diseases.